Drug-receptor interactions hydrophobic

Thus, non-covalent hydrophobic interactions, hydrogen bonds, and electrostatic bonds all contribute to the overall shape of a protein (Figure 13.3). As we shall see (Section 13.3.2), many pertinent properties of a protein are then provided by the appropriate combination of the remaining amino acid side-chains that reside on the surface, allowing specific binding to various molecules. This is the essence of enzymic activity and drug-receptor interactions. 

Formation of hydrophobic bonds between nonpolar hydrocarbon groups on the drug and those in the receptor site is also common. Although these bonds are not very specific, the interactions take place to exclude water molecules. Repulsive forces that decrease the stability of the drug-receptor interaction include repulsion of like charges and steric hindrance. 

Hydrophobicity of an inhibitor and critical micelle concentrations of the inhibitor in forming micelles have been found60 to play a significant role in the case of substituted imidazoles, imidazolines and fatty amines and these correlations do not take into account the electronic interactions. This correlation is based on Hansch s model of drug-receptor interactions based on transport of drug/inhibitor to the site followed by interaction at the site. 

Since the ir value is constitutive, the stereospecific nature of hydro-phobic bonding for drug-receptor interactions can be delineated by regression analyses with the tt values of substituents separately for each position of the congeners. Thus, the substituent effect on the emulsin hydrolysis of substituted phenylglucosides has been nicely delineated by analyzing kinetic constants separately for meta and para isomers. The meta substituents play no hydrophobic role in the enzyme-substrate complex formation 24). 

In the broadest sense, these "bonds would include covalent, ionic, hydrogen, dipole-dipole, van der Waals, and hydrophobic interactions. Most drug-receptor interactions constitute a combination of the bond types listed in Table 1.1, most of which are reversible under physiological conditions. 

In the context of drug-like substances, hydrophobicity is related to absorption, bioavailability, hydrophobic drug-receptor interactions, metabolism and toxicity. Closely related to log P is the octanol-water distribution coefficient (logDpn), accounting for partition of pH-dependent mixture of ionizable species. Ionization of any compound makes it more water soluble and then less lipophilic. The log D can be calculated from log Pand acid dissociation constant pJC, by the following expression [Cronin, Aptula et al, 2002b Livingstone, 2003] ... 

As for van der Waals forces, hydrophobic interactions are individually weak (0.1 to 0.2 kJ moF for every square angstrom of solvent-accessible hydrocarbon surface ), but the total contribution of hydrophobic bonds to drug-receptor interactions is substantial. Similarly, the overall strength of the hydrophobic interaction between two molecules is very dependent on the quality of the steric match between the two molecules. If this is not sufficiently close to squeeze all of the solvent from the interface, a substantial entropy penalty must be paid for each of the trapped water molecules. 

Parameters which encode certain structural features and properties are needed to correlate biological activities with chemical structures in a quantitative manner. Of special value are physicochemical properties which are directly related to the intermolecular forces involved in the drug-receptor interaction as well as to the transport and distribution properties of drugs. In this respect hydrophobic, polar, electronic, and steric properties are most important most often, polarizability parameters are considered as being closely related to steric parameters and are discussed together with these parameters, although they are definitely different (if structural variation is appropriate). 

The drug-receptor interaction is a highly specialized hydrophobic, polar, electronic, and steric interaction the lipophilicity pattern, the electron density distribution, and the polarizability pattern at the surface of both the drug and its binding site contribute to the interaction energy. 

Hille B (1977) Local anesthetics hydrophilic and hydrophobic pathways for the drug-receptor interaction. J Gen Physiol 69 487-515... 

One of the earliest efforts directed toward including hydrophobic effects in drug-receptor interactions is the hydropathic interaction (HINT) technique of Kellogg et al. > The HINT formalism is strongly rooted in the CLOGP... 

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